Program Information
Utilization of 18F-FDG PET/MR and 18F-FLT PET/CT to Assess Effects of Immunotherapy in Canines
M Scarpelli*, T Bradshaw , L Forrest , D Huff , S Loeber , D Vail , R Jeraj , University of Wisconsin, Madison, WI
Presentations
SU-K-601-9 (Sunday, July 30, 2017) 4:00 PM - 6:00 PM Room: 601
Purpose: Immunotherapies are now widely used for treating cancer; however, few pharmacodynamic and response-based biomarkers have been identified for assessing these therapies. This study investigates whether proliferative and metabolic changes in tumors (and lymphoid organs), as measured by quantitative imaging, may be used as biomarkers in immunotherapy.
Methods: A canine with osteosarcoma was injected with toll-receptor agonist Mifamurtide (stimulant of the innate immune system with known anti-cancer activity in canines and humans) on days 0 and +4. FDG PET/MR scans were performed on days -1 and +6; FLT PET/CT scans were performed on days 0 and +7. Tumor and lymphoid organs were identified by a veterinary radiologist and manually segmented, allowing extraction of summary SUV metrics (e.g. SUVtotal). All images were registered to the baseline FLT PET/CT, enabling assessment of changes in tumor SUVs on a voxel-level. Since infiltration of immune effector molecules/cells into the tumor causes increased inflammation/glycolysis and decreased tumor cell proliferation, change in tumor FDG/FLT SUV ratio was used to quantify an immunotherapeutic response.
Results: From baseline to follow-up, the median change in tumor voxel FDG/FLT SUV ratio was +32%. Voxel-level analysis revealed heterogeneous changes in tumor cell proliferation, with 35% of tumor voxels (112cm^3) exhibiting decreases in FLT SUV (median -31%) and 65% of voxels (210cm^3) exhibiting increases in FLT SUV (median +57%). Tumor SUVtotal changed by +6% (FLT) and +54 (FDG). Assessment of lymphoid organs revealed bone marrow (vertebrae L2–L7) SUVtotal changed +31% (FLT) and -27% (FDG).
Conclusion: Increase in FDG/FLT uptake ratio during therapy, suggests infiltration of immune effectors into tumor regions and potentially offers a much-needed biomarker to non-invasively assess immunotherapies. Although overall tumor burden (SUVtotal) increased for both tracers, a voxel-based analysis revealed tumor regions with diminished cell proliferation, underscoring the importance of developing biomarkers to assess intratumor heterogeneity during immunotherapy.
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